This project focuses on the effects of fatty acid oxidation on recovery from myocardial ischemia. Exposure of the myocardium to long chain fatty acids has long been known to increase myocardial oxygen consumption and to impair functional recovery from ischemia. For example, perhexiline, a putative inhibitor of fatty acid oxidation, is used in Europe to treat angina, and its benefits are observed in patients maximally treated with b-adrenergic blocking agents, nitrates, and calcium channel blockers. We examined the effects of perhexiline in normoxic and post-ischemic isolated rat hearts exposed to a mixture of pyruvate, lactate, _-hydroxybutyrate, acetoacetate, glucose, and long chain fatty acids. All substrates except glucose are 13C enriched. Perhexiline significantly inhibited fatty acid oxidation and stimulated the oxidation of lactate in normoxic hearts, but the effect was not sufficient to substantially change myocardial oxygen demand. In a separate study, the effects of glutamate and aspartate on metabolic pathways were examined under conditions of cardioplegia. Again, hearts were supplied with physiological substrates, but aspartate and glutamate in the presence of cardioplegic arrest did not further alter substrate utilization patterns substantially, although acetoacetate utilization was somewhat lower compared to simple cardioplegic arrest.